Search

WO-2026096713-A1 - TREATMENT OF WARM AUTOIMMUNE HEMOLYTIC ANEMIA

WO2026096713A1WO 2026096713 A1WO2026096713 A1WO 2026096713A1WO-2026096713-A1

Abstract

The present invention provides compositions and methods of treating and improving the symptoms of warm autoimmune hemolytic anemia using an antibody or antigen-binding fragment thereof that specifically binds human CD19 (e.g., obexelimab).

Inventors

  • POMA, ALLEN
  • WANG, XIAODONG
  • QUINN, Shauna
  • WELLS, Audrey
  • ZHANG, Dale
  • MATIJEVIC, Mark
  • FENG, XIAO
  • YAZDANBAKHSH, Karina

Assignees

  • ZENAS BIOPHARMA, INC.

Dates

Publication Date
20260507
Application Date
20251030
Priority Date
20241030

Claims (20)

  1. 1. A method of treating warm autoimmune hemolytic anemia (wAIHA), comprising administering obexelimab subcutaneously to a human patient at a therapeutically effective dosing regimen for a treatment period sufficient to result in at least an increase of hemoglobin (Hgb) of > 2 g/dL as compared to baseline.
  2. 2. The method of claim 1, wherein the treatment period is at least 8 weeks, at least 10 weeks, at least 15 weeks, at least 20 weeks, or at least 24 weeks.
  3. 3. The method of any one of the preceding claims, wherein the patient achieves a Hgb level of > 7 g/dL.
  4. 4. The method of any one of the preceding claims, wherein the patient achieves a Hgb level of > 10 g/dL.
  5. 5. The method of claim 3 or 4, wherein the patient maintains the Hgb level for at least 3 weeks.
  6. 6. The method of claim 5, wherein the patient maintains the Hgb level for at least 5 weeks, at least 10 weeks, at least 15 weeks, or at least 20 weeks.
  7. 7. The method of any one of the preceding claims, wherein the patient achieves one or more of the following: a) a reduction in serum lactate dehydrogenase (LDH) as compared to baseline; b) a reduction in bilirubin as compared to baseline; c) an increase in serum haptoglobin as compared to baseline.
  8. 8. The method of claim 7, wherein a patient achieves normal values of one or more of the following: a) LDH; b) bilirubin; c) haptoglobin. Attorney Docket No. ZEN-024WO1
  9. 9. A method of treating wAIHA comprising administering obexelimab to a patient at a therapeutically effective dosing regimen for a treatment period sufficient to result in reducing the level of anti-RBC autoantibodies by at least 10% as compared to baseline.
  10. 10. The method of claim 9, wherein the treatment period is at least 10 weeks, at least 15 weeks, at least 20 weeks, or at least 24 weeks.
  11. 11. The method of claim 9 or 10, wherein the therapeutically effective dosing regimen is sufficient to reduce the presence of anti-red blood cell (RBC) autoantibodies so that the patient is substantially free of anti-RBC autoantibodies.
  12. 12. The method of any one of claims 10-11, wherein the therapeutically effective dosing regimen is sufficient to reduce the presence of anti-RBC autoantibodies to an undetectable amount.
  13. 13. The method of any one of claims 10-12, wherein the patient direct anti globulin test (DAT) negative following administration of the therapeutically effective dosing regimen.
  14. 14. The method of any one of claims 10-13, comprising administering obexelimab at a dose of 250 mg.
  15. 15. The method of claim 14, comprising administering obexelimab at a dose of 250 mg weekly.
  16. 16. The method of any one of the preceding claims, wherein the patient is DAT -positive for anti-IgG and/or anti-IgA at baseline.
  17. 17. The method of any one of the preceding claims, wherein the patient, prior to administration of obexelimab, had an Hgb level of < 10 g/dL.
  18. 18. The method of any one of the preceding claims, wherein the patient, prior to administration of obexelimab, had an Hgb level of > 7. Attorney Docket No. ZEN-024WO1
  19. 19. The method of any one of the preceding claims, wherein the patient has primary wAIHA.
  20. 20. The method of any one of claims 1-18, wherein the patient has secondary wAIHA.

Description

Attorney Docket No. ZEN-024WO1 TREATMENT OF WARM AUTOIMMUNE HEMOLYTIC ANEMIA CROSS REFERENCE TO RELATED APPLICATIONS [0001] The present application claims benefit of U.S. Provisional Patent Application No. 63/713,867, filed on October 30, 2024, and U.S. Provisional Patent Application No 63/726,904 filed on December 2, 2024, each of which are hereby incorporated by reference in their entirety. SEQUENCE LISTING [0002] The instant application contains a Sequence Listing which has been submitted electronically in XML file format and is hereby incorporated by reference in its entirety. Said XML copy, created on October 21, 2024, is named “ZEN-024WOl_SL” and is 16,384 bytes. BACKGROUND [0003] Autoimmune hemolytic anemia (AH4A) is an uncommon, acquired autoimmune disorder, in which autoantibodies directed against self-red blood cell (RBC) membrane antigens lead to accelerated destruction of RBCs. The destruction of the RBCs by immune cells more rapidly than the production rate of production of new cells, leads apatients to develop anemia, generalized fatigue, dizziness, syncope, malaise, chest pressure/pain, cognitive dysfunction, weakness, a pale skin color (pallor), palpitations, shortness of breath (dyspnea), appearance of jaundice and abnormally dark urine (hematouria), usually suggestive of hemolysis. Murine models of AH4A show that reticulocytes are preferentially targeted by anti-RBC autoantibodies and an increase in oxidative stress may trigger autoantibody production. Though not usually fatal, most patients have a reduced health-related quality of life. Among the forms of AH4A, warm AH4A (wAIHA) is the most prevalent. Current therapies used for treatment of wAIHA include steroids, immunosuppressants and splenectomy. Corticosteroids are commonly used as first- line treatment but are not always effective. Additionally, prolonged steroid use carries a significant risk for infection, diabetes, and fracture. Harnessing treatment and defining a risk- adapted efficacious therapy for wAIHA is an emerging unmet need. Attorney Docket No. ZEN-024WO1 SUMMARY [0004] Among other things, the present disclosure provides methods, compositions, and uses of an anti-CD19 antibody such as obexelimab for efficient treatment of a patient with wAIHA and prevention of relapse. In some aspects, the present invention provides a method of treating wAIHA, comprising administering obexelimab at a therapeutically effective dosing regimen to improve hemoglobin (Hgb) as compared to baseline. In some aspects, the present invention provides a method of treating wAIHA, comprising administering obexelimab at a therapeutically effective dosing regimen to reduce anti-RBC autoantibodies as compared to baseline. In some embodiments, the present disclosure is directed to a method of treating of wAIHA using CD 19 antibodies such as obexelimab. [0005] In some aspects, the present invention provides a method of treating wAIHA, including administering obexelimab subcutaneously to a patient at a therapeutically effective dosing regimen for a treatment period sufficient to result in an increase of Hgb of > 2 g/dL as compared to baseline. [0006] In some embodiments, a treatment period is at least 8 weeks, at least 10 weeks, at least 15 weeks, at least 20 weeks, or at least 24 weeks. [0007] In some embodiments, a patient achieves a Hgb level of > 7 g/dL. In some embodiments, a patient achieves a Hgb level of > 8 g/dL. In some embodiments, a patient achieves a Hgb level of > 9 g/dL. In some embodiments, a patient achieves a Hgb level of > 10 g/dL. In some embodiments, a patient maintains the Hgb level for at least 5 weeks, at least 10 weeks, at least 15 weeks, or at least 20 weeks. [0008] In some embodiments, a patient achieves one or more of the following: (a) a reduction in serum lactate dehydrogenase (LDH) as compared to baseline; (b) a reduction in bilirubin as compared to baseline; and (c) an increase in serum haptoglobin as compared to baseline. In some embodiments, a patient achieves normal values of one or more of the following: (a) LDH; (b) bilirubin; and (c) haptoglobin. [0009] In some aspects, the present invention provides a method of treating wAIHA including administering obexelimab to a patient at a therapeutically effective dosing regimen for a treatment period sufficient to result in reducing the level of anti-RBC autoantibodies by at least 10% as compared to baseline. Attorney Docket No. ZEN-024WO1 [0010] In some embodiments, a treatment period is at least 8 weeks, at least 10 weeks, at least 15 weeks, at least 20 weeks, or at least 24 weeks. [0011] In some embodiments, a therapeutically effective dosing regimen is sufficient to reduce the presence of anti-RBC autoantibodies so that the patient is substantially free of anti-RBC autoantibodies. In some embodiments, a therapeutically effective dosing regimen is sufficient to reduce the presence of anti-RBC autoantibodies to an undetectable amount. [0012] In some embodiments, a patient i